Ultra-thin elastin-based membranes as an innovative dressing to enhance skin wound healing

The development of advanced wound dressings that combine mechanical compliance, bioactivity, and controlled biodegradability remains an unmet need in skin regeneration, particularly for chronic and complex wounds where cell-cell and cell-extracellular matrix (ECM) interactions are severely disrupted. Here, we report the development of ultra-thin, highly compliant elastin-like recombinamer (ELR) membranes designed as ECM-mimetic wound dressings that actively support tissue regeneration. The membranes are fabricated via a catalyst-free click-chemistry reaction at a liquid-liquid interface, enabling tuneable thickness (5-25 μm), surface topography, wettability, and enzymatic degradability. <i>In vitro</i> studies utilising human fibroblasts and keratinocytes demonstrate sustained viability, adhesion, and proliferation over 21 days, accompanied by enhanced cell migration and maturation, as substantiated by scratch assays and gene expression analyses<i>. Ex vivo</i> evaluation in a human skin wound model reveals accelerated re-epithelialization without tissue contraction. <i>In vivo</i>, ELR membranes demonstrate prolonged stability and optimal biocompatibility following subcutaneous implantation, with no evidence of fibrosis or foreign body reaction. In a full-thickness murine excisional wound model, membrane-treated wounds display enhanced healing dynamics and reduced contraction compared with control treatments. This is accompanied by favourable modulation of the local immune response, characterised by a shift towards a pro-regenerative macrophage phenotype. Overall, these findings establish ultra-thin ELR membranes as a versatile, biodegradable, and biologically instructive wound dressing platform that promotes intrinsic tissue regeneration without the need for exogenous growth factors or cells. This strategy represents a promising therapeutic approach for enhancing skin regeneration in demanding clinical settings applications.